Field of the Invention and Related Art Statement
The present invention relates to a method of detecting and judging a particle agglutination pattern for use in diagnosis.
There has been developed an apparatus for analyzing a blood sample by detecting a particle agglutination pattern formed on a reaction vessel having an inclined bottom surface. Such an apparatus is described in, for instance U.S. Pat. No. 4,727,033 issued to K. Hijikata et al on Feb. 23, 1988. In this apparatus, a test liquid is formed in a conical reaction vessel by supplying a blood sample, i.e. blood cell sample or serum sample and a reagent, i.e. serum reagent or sensitized particle reagent into the reaction vessel, and then the reaction vessel containing the test liquid is kept still for a predetermined reaction time such as thirty minutes. During the reaction time, particles in the test liquid descend onto the inclined bottom surface. When the particles are agglutinated with each other, there is formed a uniformly agglutinated layer of the particles on the bottom surface, but when the particles are not agglutinated with each other, the particles roll down along the inclined bottom surface and are collected at the lowest bottom center to form a center dot. Then, the particle pattern formed on the bottom surface of the reaction vessel is photoelectrically detected by projecting light from one side of the reaction vessel and light transmitted through the reaction vessel is received by a photodetector. In FIG. 10 of the above mentioned U.S. Pat. No. 4,727,033, there is disclosed a photodetector having two concentrical light receiving regions, one for receiving light passing through a central portion of the reaction vessel and the other for receiving light transmitted through a peripheral portion of the reaction vessel. By processing output signals supplied from these light receiving regions, it is possible to judge whether the particle pattern is of the agglutinated pattern or non-agglutinated pattern. That is to say, when the particles are agglutinated with each other, there is not a significant difference between the output signals from the two light receiving regions, but when the non-agglutinated particle pattern is formed, the light passing through the central portion of the reaction vessel becomes weaker than the light transmitted through the peripheral portion, so that there is produced a large difference between the output signals supplied from the two light receiving regions. Therefore, by deriving a ratio of the output signal from the central light receiving region to the output signal from the peripheral light receiving region and comparing the ratio with predetermined upper and lower thresholds, the particle pattern formed on the inclined bottom surface can be judged and the sample blood can be analyzed. That is to say, when the ratio is greater than the upper threshold value, it is judged that the agglutination occurs, and when the ratio is smaller than the lower threshold value, it is judged that the agglutination does not occur. When the measured ratio is within the upper and lower threshold values, it is judged that the particle patter could not be judged certainly. It has been experimentally confirmed that the known method of judging the particle patter is suitable for judging true or typical particle patterns. However, in the actual analysis there are sometimes produced particle patterns which could no be judged definitely by the known method. In such a case, there is generated an automatic analysis result representing that the relevant sample could not be determined definitely, so that the sample has to be analyzed visually with naked eyes or has to be tested again. It has been found that the known method has the reexamination rate of about 20%. That is to say, when a hundred samples are tested, about twenty samples have to be subjected to the examination. In order to increase the efficiency of the analysis, it is desired to reduce the number of samples which should be analyzed again. In the known method, this may be effected by changing the threshold values for use in the comparison. However, then the accuracy of the analysis would be reduced, and the agglutinated pattern might be judged as the non-agglutinated pattern and the non-agglutination pattern might be judged as the agglutination pattern. Such an erroneous judgment would result in a serious problem and should be avoided particularly in the blood transportation. In case of analyzing infectious diseases, i.e. in case of detecting whether or not a sample is infected by various kinds of antigens such as Hb antigens including HBsAg, HBsAb, HBcAg, HBcAb, HBeAg and HBeAb, ATLA, HIV(AIDS) and CMV, it would be necessary to enhance the sensitivity of agglutination, because the agglutinating force of these antigens is very weak. To this end, an amount of the reagent has to be made large, carriers of reagents have to be light in weight and the reaction time has to be made longer. Then, the non-agglutinated particles do not roll down along the inclined bottom surface promptly and the non-agglutinated particle pattern in which a large amount of particles are collected in the lowest central portion of the reaction vessel could not be formed correctly, so that the non-agglutinated pattern might be judged as the agglutinated pattern. Further, the cost of analysis is liable to increase remarkably and the efficiency of analysis becomes low to a great extent. In order to reduce the analyzing cost and time, an amount of the reagent has to be decreased and reagent carriers having heavy weight have to be used. In order to avoid such a problem, the threshold values have to be set such that particle patterns which could not be definitely judged are classified into an uncertain group and samples producing such uncertained particle patterns are analyzed visually with naked eyes or tested again with a different method, i.e. manual operation. In this manner, in the known agglutination analyzing method, the above mentioned contracting problems could not be solved. The above mentioned problems equally occur in the blood type analysis such as ABO, Rh and ABS (irregular antigen screening).
Further, in case of analyzing the above mentioned antigens having the weak agglutination force, such abnormal conditions have been sometimes experienced that a part of the uniformly deposited particle pattern is peeled from the bottom surface of the reaction vessel, and the center dot of the deposited particle pattern becomes small in size, unclear in sharpness or donut-like in shape. Then, the agglutinated particle pattern might be erroneously judged as the non-agglutinated pattern. This might also cause serious problems.